Clofazimine, a Promising Drug for the Treatment of Babesia microti Infection in Severely Immunocompromised Hosts.

Abstract

BACKGROUND:

Persistent and relapsing babesiosis caused by Babesia microti often occurs in immunocompromised patients, and has been associated with resistance to antimicrobial agents such as atovaquone. Given the rising incidence of babesiosis in the United States, novel drugs are urgently needed. In the current study, we tested whether clofazimine (CFZ), an antibiotic used to treat leprosy and drug-resistant tuberculosis, is effective against B. microti.

METHODS:

Mice with severe combined immunodeficiency were infected with 107B. microti-infected erythrocytes. Parasites were detected by means of microscopic examination of Giemsa-stained blood smears or nested polymerase chain reaction. CFZ was administered orally.

RESULTS:

Uninterrupted monotherapy with CFZ curtailed the rise of parasitemia and achieved radical cure. B. microti parasites and B. microti DNA were cleared by days 10 and 50 of therapy, respectively. A 7-day administration of CFZ delayed the rise of parasitemia by 22 days. This rise was caused by B. microti isolates that did not carry mutations in the cytochrome b gene. Accordingly, a 14-day administration of CFZ was sufficient to resolve high-grade parasitemia caused by atovaquone-resistant B. microti parasites.

CONCLUSIONS:

Clofazimine is effective against B. microti infection in the immunocompromised host. Additional preclinical studies are required to identify the minimal dose and dosage of CFZ for babesiosis.

• Authors: Bumduuren Tuvshintulga, Edouard Vannier, Dickson S Tayebwa, Sambuu Gantuya, Thillaiampalam Sivakumar, Azirwan Guswanto, Peter J Krause, Naoaki Yokoyama, Ikuo Igarashi
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 222 Issue 6 Pg. 1027-1036 (08 17 2020) ISSN: 1537-6613 [Electronic] United States
• PMID: 32310272 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

Chemical References

• DNA, Protozoan
• Leprostatic Agents
• Cytochromes b
• Clofazimine

Topics

• Amino Acid Sequence
• Animals
• Babesia microti (drug effects, genetics, immunology)
• Babesiosis (drug therapy, immunology, parasitology)
• Clofazimine (administration & dosage, adverse effects, therapeutic use)
• Cytochromes b (chemistry, genetics)
• DNA, Protozoan
• Disease Models, Animal
• Drug Evaluation, Preclinical
• Drug Resistance
• Erythrocytes (parasitology)
• Immunocompromised Host
• Leprostatic Agents (administration & dosage, adverse effects, therapeutic use)
• Mice
• Parasitemia (parasitology)
• Treatment Outcome